Hydrophobic, hydrophilic and other interactions in epitope-paratope binding

Macroscopic, non-covalent, aspecific interactions between hydrophilic biopolymers, particles and cells in aqueous media tend to be repulsive; they are caused by Lifshitz-van der Waals (LW), Lewis acid-base (AB) and electrostatic (EL) forces. Microscopic scale specific interactions, e.g. between epitopes and paratopes, are also non-covalent and caused by attractive LW, AB and EL forces, which locally must be able to overcome the long- to medium-range macroscopic aspecific repulsive forces. Thus epitopes and paratopes need to be able to attract each other over a distance of at least 3 nm. The medium- and long-range specific attractive forces are mainly of hydrophobic (AB) and of EL origin; in aqueous media the medium- and long-range LW attractions are usually much weaker. It has been shown that hydrophobic (AB) interactions are as often enthalpic as entropic. Upon expulsion of interstitial water of hydration between epitope and paratope, a strong interfacial bond ultimately arises which is mainly caused by LW forces.